Transient genome-wide transcriptional response to low-dose ionizing radiation in vivo in humans.

Purpose: The in vivo effects of low-dose low linear energy transfer ionizing radiation on healthy human skin are largely unknown. Using a patient-based tissue acquisition protocol, we have performed a series of genomic analyses on the temporal dynamics over a 24-hour period to determine the radiation response after a single exposure of 10 cGy.

Methods And Materials: RNA from each patient tissue sample was hybridized to an Affymetrix Human Genome U133 Plus 2.

Selecting an intervention time for intravascular enzymatic cleavage of peptide linkers to clear radioisotope from normal tissues.

Unlabelled: Protease degradable linkers have been proposed to improve the therapeutic index (TI) (i.e., tumor to normal tissue) of molecular targeted radioisotope therapy by reducing unbound radiotargeting agent in the blood and other normal tissues.

Dosimetry for quantitative analysis of the effects of low-dose ionizing radiation in radiation therapy patients.

We have developed and validated a practical approach to identifying the location on the skin surface that will receive a prespecified biopsy dose (ranging down to 1 cGy) in support of in vivo biological dosimetry in humans. This represents a significant technical challenge since the sites lie on the patient's surface outside the radiation fields. The PEREGRINE Monte Carlo simulation system was used to model radiation dose delivery, and TLDs were used for validation on phantoms and for confirmation during patient treatment.

Radiation phantom with humanoid shape and adjustable thickness (RPHAT).

A new radiation phantom with humanoid shape and adjustable thickness (RPHAT) has been developed. Unlike the RANDO phantom which is a fixed thickness, this newly designed phantom has adjustable thickness to address the range of thicknesses of real-world patients. RPHAT allows adjustment of the body thickness by being sliced in the coronal (instead of axial) direction.

Enhanced therapeutic index of radioimmunotherapy (RIT) in prostate cancer patients: comparison of radiation dosimetry for 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-peptide versus 2IT-DOTA monoclonal antibody linkage for RIT.

Purpose: Radioimmunotherapy delivered by radiometal immunoconjugates and followed by marrow support is dose limited by deposition of radioactivity in normal organs. To increase elimination of radioactivity from the liver and body and, thus, minimize hepatic radiation dose, a peptide having a specific cathepsin B cleavage site was placed between the radiometal chelate DOTA (1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid) and the monoclonal antibody m170, and the comparative pharmacokinetics was evaluated in prostate cancer patients.

Experimental Design: (111)In-DOTA-2IT-m170 and (111)In-DOTA-peptide-(GGGF)-m170, representing the same monoclonal antibody and chelate with and without the cleavable linkage, were studied in comparable groups of prostate cancer patients (17 with In-2IT-BAD-m170 and 8 with In-DOTA-peptide-m170).

Impact of nodal regression on radiation dose for lymphoma patients after radioimmunotherapy.

Unlabelled: Radioimmunotherapy for non-Hodgkin's lymphoma often results in surprisingly high response rates compared with those expected from estimated absorbed radiation doses. Several factors, including radiobiologic response, selective targeting, and heterogeneous absorbed radiation within the lymphoma, are likely to contribute to the lack of a dose-response relationship. This article investigates the impact of nodal regression on absorbed radiation dose and applies a correction factor to account for its effect.

Application of MINERVA Monte Carlo simulations to targeted radionuclide therapy.

Recent clinical results have demonstrated the promise of targeted radionuclide therapy for advanced cancer. As the success of this emerging form of radiation therapy grows, accurate treatment planning and radiation dose simulations are likely to become increasingly important. To address this need, we have initiated the development of a new, Monte Carlo transport-based treatment planning system for molecular targeted radiation therapy as part of the MINERVA system.

Radiation dosimetry for radionuclide therapy in a nonmyeloablative strategy.

Radionuclide therapy extends the usefulness of radiation from localized disease of multifocal disease by combining radionuclides with disease-seeking drugs, such as antibodies or custom-designed synthetic agents. Like conventional radiotherapy, the effectiveness of targeted radionuclides is ultimately limited by the amount of undesired radiation given to a critical, dose-limiting normal tissue, most often the bone marrow. Because radionuclide therapy relies on biological delivery of radiation, its optimization and characterization are necessarily different than for conventional radiation therapy.